PROCESS MODELLING AND DEBOTTLENECKING STUDY OF A VACCINE PRODUCTION

ABSTRACT: The main objective of this research work was to model and optimise the production of a locally-developed Infectious Coryza (IC) vaccine. The simulation work was performed using a commercially available batch process simulator SuperPro Designer v5.5. Six debottlenecking schemes were analysed using throughput analysis and cost to benefit ratio (CBR) when the annual production was set to increase by 100%. Based on the economic analysis, the selected debottlenecking scheme has an annual predicted revenue of USD 240 million, with a gross margin of 9.13% and a return on investment (ROI) of 46.12%. In addition, the payback period of the selected scheme is estimated to be within three years.  ABSTRAK: Objektif utama dalam penyelidikan ini adalah untuk memodelkan dan mengoptimumkan hasil pembuatan vaksin tempatan Coryza berjangkit. Kerja simulasi ini dijalankan menggunakan alat simulasi Super Pro Designer v5.5. Sebanyak enam (6) skema khusus diujikaji menggunakan analisis pemprosesan dan kos kepada nisbah faedah (CBR) apabila pembuatan tahunan meningkat kepada 100%. Berdasarkan analisis ekonomi yang telah dilakukan, sesuatu skema khusus yang dipilih mempunyai keuntungan sebanyak USD 240 juta dengan margin kasar 9.13% dan pulangan atas pelaburan (ROI) sebanyak 46.12%. Selain itu juga, tempoh pembayaran balik bagi skema yang dipilih dianggarkan dalam tempoh tiga(3) tahun. KEYWORDS: process simulation; modelling; debottlenecking; optimisatio

Ultrasound assisted extraction of nano calcium from waste eggshell: a preliminary study on crystal violet dye removal

Extraction of bio-based calcium carbonate (CaCO3) nanoparticles from eggshell waste materials assisted by horn-type ultrasonic generator was studied. Chicken eggshells (CS) and duck eggshells (DS) were cleaned and ground using pestle and mortar, and further treated with acetone and dichloromethane (DCM) to remove impurities. The treated eggshells were then ultrasonic irradiated for 5 to 20 min, before sending to Dynamic Light Scattering (DLS) for particle size distribution measurement. Results shown that, nano calcium with approximately 300 nm was being recovered successfully. The recovered nano calcium is later subjected to Crystal Violet (CV) dye removal testing and has recorded a high removal efficiency of up to 87.90 % and 83.06 % for DS and CS, respectively. The high removal efficiency is basically due to the large surface area on calcium nanoparticles created by ultrasonic cavitation, as confirmed by Scanning Electron Microscopy (SEM) analysis

Chemokine-driven lymphocyte infiltration: an early intratumoural event determining long-term survival in resectable hepatocellular carcinoma

Objective Hepatocellular carcinoma (HCC) is a heterogeneous disease with poor prognosis and limited methods for predicting patient survival. The nature of the immune cells that infiltrate tumours is known to impact clinical outcome. However, the molecular events that regulate this infiltration require further understanding. Here the ability of immune genes expressed in the tumour microenvironment to predict disease progression was investigated.MethodsUsing quantitative PCR, the expression of 14 immune genes in resected tumour tissues from 57 Singaporean patients was analysed. The nearest-template prediction method was used to derive and test a prognostic signature from this training cohort. The signature was then validated in an independent cohort of 98 patients from Hong Kong and Zurich. Intratumoural components expressing these critical immune genes were identified by in situ labelling. Regulation of these genes was analysed in vitro using the HCC cell line SNU-182.ResultsThe identified 14 immune-gene signature predicts patient survival in both the training cohort (p=0.0004 and HR=5.2) and the validation cohort (p=0.0051 and HR=2.5) irrespective of patient ethnicity and disease aetiology. Importantly, it predicts the survival of patients with early disease (stages I and II), for whom classical clinical parameters provide limited information. The lack of predictive power in late disease stages III and IV emphasises that a protective immune microenvironment has to be established early in order to impact disease progression significantly. This signature includes the chemokine genes CXCL10, CCL5 and CCL2, whose expression correlates with markers of T helper 1 (Th1), CD8(+) T and natural killer (NK) cells. Inflammatory cytokines (tumour necrosis factor α, interferon γ) and Toll-like receptor 3 ligands stimulate intratumoural production of these chemokines which drive tumour infiltration by T and NK cells, leading to enhanced cancer cell death.ConclusionA 14 immune-gene signature, which identifies molecular cues driving tumour infiltration by lymphocytes, accurately predicts survival of patients with HCC especially in early disease

Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals

Introduction: Human APOBEC3G/F (hA3G/F) restricts retroviral replication through G-to-A hypermutations, which can generate drug-resistant progenies in vitro. The clinical relevance is still inconclusive. To bridge this gap, we aim to study the role of these hypermutations in evolution of drug resistance; we characterised hA3G/F-mediated hypermutations in the RT region of the pol gene of patients with or without antiretroviral therapy (ART). Methods: In 88 HIV-1-positive individuals, drug resistance genotyping was carried out in plasma virus and provirus by population sequencing. Hypermutations were determined by three different approaches using Hypermut 2.0 software, cluster analysis and APOBEC3G-mediated defectives indices. Clinical and demographic characteristics of these individuals were studied in relation to these hypermutations. Results: hA3G/F-mediated hypermutated sequences in proviral DNA, but not in plasma virus, were identified in 11.4% (10/88) subjects. Proviral hypermutations were observed more frequently in patients with ART failure than in ART-naïve individuals (p=0.03). In therapy failure patients, proviral hypermutation were associated with greater intra-compartmental genetic diversity (p<0.001). In therapy-naïve individuals, hypermutated proviral DNA with M184I and M230I mutations due to the editing of hA3G, had stop codons in the open reading frames and the same mutations were absent in the plasma virus. Only a limited concordance was found between the drug resistance mutations in plasma RNA and proviral DNA. Conclusions: hA3G lethal hypermutation was significantly associated with ART failure in Indian HIV-1 subtype C patients. It is unlikely that viral variants, which exhibit hypermutated sequences and M184I and/or M230I, will mature and expand in vivo

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

The emotional context of self-management in chronic illness: A qualitative study of the role of health professional support in the self-management of type 2 diabetes

Background: Support for patient self-management is an accepted role for health professionals. Little evidence exists on the appropriate basis for the role of health professionals in achieving optimum self-management outcomes. This study explores the perceptions of people with type 2 diabetes about their self-management strategies and how relationships with health professionals may support this.Methods: Four focus groups were conducted with people with type 2 diabetes:&nbsp; two with English speaking and one each with Turkish and Arabic-speaking. Transcripts from the groups were analysed drawing on grounded hermeneutics and interpretive description.Results: We describe three conceptually linked categories of text from the focus groups based on emotional context of self management, dominant approaches to self management and support from health professionals for self management. All groups described important emotional contexts to living with and self-managing diabetes and these linked closely with how they approached their diabetes management and what they looked for from health professionals. Culture seemed an important influence in shaping these linkages.Conclusion: Our findings suggest people construct their own individual self-management and self-care program, springing from an important emotional base. This is shaped in part by culture and in turn determines the aims each&nbsp; person has in pursuing self-management strategies and the role they make available to health professionals to support them. While health professionals\u27&nbsp; support for self-care strategies will be more congruent with patients\u27 expectations if they explore each person\u27s social, emotional and cultural circumstances, pursuit of improved health outcomes may involve a careful balance between supporting as well as helping shift the emotional constructs surrounding a patient life with diabetes.<br /

A generalized invariant imbedding equation II

Research into fetal development and medicin

Post-acute COVID-19 outcomes including participant-reported long COVID: amubarvimab/romlusevimab versus placebo in the ACTIV-2 trial

BackgroundIt is unknown if early COVID-19 monoclonal antibody (mAb) therapy can reduce risk of Long COVID. The mAbs amubarvimab/romlusevimab were previously demonstrated to reduce risk of hospitalization/death by 79%. This study assessed the impact of amubarvimab/romlusevimab on late outcomes, including Long COVID.MethodsNon-hospitalized high-risk adults within 10 days of COVID-19 symptom onset enrolled in a randomized, double-blind, placebo-controlled phase 2/3 trial of amubarvimab/romlusevimab for COVID-19 treatment. Late symptoms, assessed using a participant-completed symptom diary, were a pre-specified exploratory endpoint. The primary outcome for this analysis was the composite of Long COVID by participant self-report (presence of COVID-19 symptoms as recorded in the diary at week 36) or hospitalization or death by week 36. Inverse probability weighting (IPW) was used to address incomplete outcome ascertainment, giving weighted risk ratios (wRR) comparing amubarvimab/romlusevimab to placebo.FindingsParticipants received amubarvimab/romlusevimab (n&nbsp;=&nbsp;390) or placebo (n&nbsp;=&nbsp;390) between January and July 2021. Median age was 49 years, 52% were female, 18% Black/African American, 49% Hispanic/Latino, and 9% COVID-19-vaccinated at entry. At week 36, 103 (13%) had incomplete outcome ascertainment, and 66 (17%) on amubarvimab/romlusevimab and 92 (24%) on placebo met the primary outcome (wRR&nbsp;=&nbsp;0.70, 95% confidence interval (CI) 0.53-0.93). The difference was driven by fewer hospitalizations/deaths with amubarvimab/romlusevimab (4%) than placebo (13%). Among 652 participants with available diary responses, 53 (16%) on amubarvimab/romlusevimab and 44 (14%) on placebo reported presence of Long COVID.InterpretationAmubarvimab/romlusevimab treatment, while highly effective in preventing hospitalizations/deaths, did not reduce risk of Long COVID. Additional interventions are needed to prevent Long COVID.FundingNational Institute of Allergy and Infectious Diseases of the National Institutes of Health. Amubarvimab and romlusevimab supplied by Brii Biosciences

Personalized mechanical ventilation guided by ultrasound in patients with acute respiratory distress syndrome (PEGASUS): study protocol for an international randomized clinical trial

background acute respiratory distress syndrome (ARDS) is a frequent cause of hypoxemic respiratory failure with a mortality rate of approximately 30%. Identifying ARDS subphenotypes based on "focal" or "non-focal" lung morphology has the potential to better target mechanical ventilation strategies of individual patients. however, classifying morphology through chest radiography or computed tomography is either inaccurate or impractical. Lung ultrasound (LUS) is a non-invasive bedside tool that can accurately distinguish "focal" from "non-focal" lung morphology. We hypothesize that LUS-guided personalized mechanical ventilation in ARDS patients leads to a reduction in 90-day mortality compared to conventional mechanical ventilation. methods the personalized mechanical ventilation guided by ultrasound in patients with acute respiratory distress syndrome (PEGASUS) study is an investigator-initiated, international, randomized clinical trial (RCT) that plans to enroll 538 invasively ventilated adult intensive care unit (ICU) patients with moderate to severe ARDS. eligible patients will receive a LUS exam to classify lung morphology as "focal" or "non-focal". thereafter, patients will be randomized within 12 h after ARDS diagnosis to receive standard care or personalized ventilation where the ventilation strategy is adjusted to the morphology subphenotype, i.e., higher positive end-expiratory pressure (PEEP) and recruitment maneuvers for "non-focal" ARDS and lower PEEP and prone positioning for "focal" ARDS. the primary endpoint is all-cause mortality at day 90. secondary outcomes are mortality at day 28, ventilator-free days at day 28, ICU length of stay, ICU mortality, hospital length of stay, hospital mortality, and number of complications (ventilator-associated pneumonia, pneumothorax, and need for rescue therapy). after a pilot phase of 80 patients, the correct interpretation of LUS images and correct application of the intervention within the safe limits of mechanical ventilation will be evaluated. discussion PEGASUS is the first RCT that compares LUS-guided personalized mechanical ventilation with conventional ventilation in invasively ventilated patients with moderate and severe ARDS. If this study demonstrates that personalized ventilation guided by LUS can improve the outcomes of ARDS patients, it has the potential to shift the existing one-size-fits-all ventilation strategy towards a more individualized approach. trial registration the PEGASUS trial was registered before the inclusion of the first patient, https://clinicaltrials.gov/ (ID: NCT05492344)